There are many drugs known to be useful for treatment of afflictions or protection of mucous membranes, e.g., for ocular diseases. A practical problem in connection with therapeutic or protective application of pharmaceutically active chemicals to afflicted mucous membranes resides in the delivery of the chemical or drug to the affected area in need of treatment. Various formulations and techniques have been attempted to deliver medicaments to mucous membranes, but there is a need for improved pharmaceutical vehicles for delivery of drugs, and it is this need to which the present invention is addressed.
For example, drugs have been formulated into aqueous solutions. However, the fleeting presence and poor contact of aqueous solutions applied to mucous membranes has been a disadvantage. The only adequate application of medication in solution form to mucous membranes is usually accomplished by employing continuous lavage or interrupted irrigation. This approach is often wasteful of expensive drugs and poses a major problem of inconvenience. Thus, treatment of severe keratoconjunctivitis sicca with isotonic salt solutions requires ocular instillation every 15-30 minutes.
The use of viscous aqueous solutions is usually more convenient. For example, the aforementioned isotonic salt solutions can often be applied every 1-2 hours and accomplish the same therapeutic objective if the solution is made viscous. Drugs have been formulated into aqueous suspensions made viscous by the addition of gums or cellulose-modified synthetic derivatives or incorporated into oleaginous vehicles or bases consisting of natural plant or animal fats or modifications thereof or petroleum-derived hydrocarbons.
Indeed, aqueous vehicles which are thickened by the addition of selected gums or cellulose-derived viscosity building agents are perhaps the most commonly used media for delivery of drugs or medicaments to mucous membranes. Generally, the viscosity of such preparation ranges from about 25 cps to indeterminate values in stiff gels. Nearly uniform drug delivery is possible with such vehicles, and they frequently provide desirable protection to the mucous membranes.
In contrast, non-viscous aqueous suspensions have many disadvantages and are not typically used. A major problem is rapid settling of the suspended drug. This gives rise to undesirable need for continuous stirring during administration in order to deliver a uniform dose.
While thick gels would seem to offer the best potential in terms of protection as well as holding and delivering medication, they in fact have some disadvantages. In some instances, they are difficult to apply from their respective commercial containers. Moreover, thick gels do not spread readily over the area being treated, and possibly painful spreading and rubbing may be necessary. Also, on evaporation of the water from the vehicle, a cosmetically unappealing hard granular or flaky residue often results at the site of the application.
Attempts to use oily vehicles to increase drug delivery and prolong ensuing pharmacologic action have not met with uniform success. The use of oleaginous vehicles, whether anhydrous or in emulsion form (oil-in-water or water-in-oil), may have advantages for certain therapeutic indications, if the vehicle will adhere. However, since normal mucous membranes are always moist with aqueous tissue fluids, and water does not mix readily with oil bases, application, uniform spreading, and retention all become difficult. Perhaps the only time oily or emulsion vehicles are used successfully is when the mucous tissue is abnormally dry because of disease.
Another approach to the delivery of drugs or medicaments to mucous membranes is the recent development of silicone plastic devices which deliver drugs at predetermined, nearly uniform, zero order rates extending from a few days to several years. However, the usefulness of such devices depends upon a constant supply of tissue fluid or glandular secretion; in the absence of fluid, plastic devices are not operative. Such devices are not designed to offer any protection to an inflamed mucous membrane. Discomfort often associated with the devices, and inadvertent loss of the devices, are additional problems.
The existence of all these disparate approaches to drug delivery to mucous membranes evidences the need for new pharmaceutical vehicles. Against the background of this array of formulations and devices with all their attendant problems, the present invention fills that need.